0 10 Inhibition Inhibition NNP 11 13 of of IN 14 18 p105 p105 NN 19 29 processing processing NN 30 32 by by IN 33 42 NF-kappaB NF-kappaB NNP 43 51 proteins protein NNS 52 54 in in IN 55 66 transiently transiently RB 67 78 transfected transfecte VBN 79 84 cells cell NNS 84 85 . . . 87 97 Regulation regulation NN 98 100 of of IN 101 104 the the DT 105 118 transcription transcription NN 119 125 factor factor NN 126 135 NF-kappaB nf-kappab NN 136 144 involves involve VBZ 145 164 proteasome-mediated proteasome-mediated JJ 165 175 processing processing NN 176 178 of of IN 179 182 the the DT 183 193 NF-kappaB1 nf-kappab1 NN 194 198 p105 p105 NN 199 208 precursor precursor NN 209 216 protein protein NN 216 217 , , , 218 223 which which WDT 224 233 generates generate VBZ 234 237 the the DT 238 241 p50 p50 NN 242 249 subunit subunit NN 250 252 of of IN 253 262 NF-kappaB NF-kappaB NNP 262 263 . . . 264 267 The the DT 268 278 processing processing NN 279 281 of of IN 282 286 p105 p105 NN 287 293 occurs occur VBZ 294 308 constitutively constitutively RB 309 311 in in FW 312 316 vivo vivo FW 317 320 but but CC 321 324 can can MD 325 327 be be VB 328 336 markedly markedly RB 337 345 enhanced enhance VBN 346 348 by by IN 349 356 various various JJ 357 365 cellular cellular JJ 366 376 activation activation NN 377 383 agents agent NNS 383 384 , , , 385 393 although although IN 394 397 the the DT 398 408 underlying underlying JJ 409 419 regulatory regulatory JJ 420 429 mechanism mechanism NN 430 432 is be VBZ 433 436 not not RB 437 440 yet yet RB 441 446 clear clear JJ 446 447 . . . 448 450 In in IN 451 454 the the DT 455 462 present present JJ 463 468 study study NN 468 469 , , , 470 472 we we PRP 473 484 demonstrate demonstrate VBP 485 489 that that IN 490 505 signal-mediated signal-mediated JJ 506 515 induction induction NN 516 518 of of IN 519 523 p105 p105 NN 524 534 processing processing NN 535 537 in in IN 538 543 human human JJ 544 545 T t NN 546 551 cells cell NNS 552 554 is be VBZ 555 565 associated associate VBN 566 570 with with IN 571 573 de de FW 574 578 novo novo FW 579 588 synthesis synthesis NN 589 591 of of IN 592 596 this this DT 597 606 precursor precursor NN 607 614 protein protein NN 614 615 . . . 616 625 Transient transient JJ 626 638 transfection transfection NN 639 646 studies study NNS 647 656 performed perform VBN 657 659 in in IN 660 664 COS7 cos7 NN 665 670 cells cell NNS 671 679 revealed reveal VBD 680 684 that that IN 685 688 the the DT 689 694 newly newly RB 695 706 synthesized synthesize VBN 707 711 p105 p105 NN 712 719 protein protein NN 720 727 appears appear VBZ 728 730 to to TO 731 733 be be VB 734 738 more more RBR 739 746 rapidly rapidly RB 747 756 processed process VBD 757 765 compared compare VBN 766 768 to to TO 769 772 its its PRP$ 773 784 accumulated accumulated JJ 785 789 form form NN 790 794 that that WDT 795 797 is be VBZ 798 805 already already RB 806 816 associated associate VBN 817 821 with with IN 822 825 the the DT 826 835 processed process VBN 836 843 product product NN 844 847 p50 p50 NN 847 848 . . . 849 862 Interestingly interestingly RB 862 863 , , , 864 867 the the DT 868 878 processing processing NN 879 883 rate rate NN 884 886 of of IN 887 891 p105 p105 NN 892 894 is be VBZ 895 903 markedly markedly RB 904 913 inhibited inhibit VBN 914 916 in in IN 917 922 cells cell NNS 923 937 co-transfected co-transfecte VBN 938 942 with with IN 943 946 p50 p50 NN 947 949 or or CC 950 955 other other JJ 956 965 NF-kappaB nf-kappab NN 966 974 subunits subunit NNS 974 975 , , , 976 985 including include VBG 986 990 RelA RelA NNP 991 994 and and CC 995 1000 c-Rel c-rel NN 1000 1001 , , , 1002 1006 that that WDT 1007 1017 physically physically RB 1018 1026 interact interact VBP 1027 1031 with with IN 1032 1036 p105 p105 NN 1036 1037 . . . 1038 1043 These these DT 1044 1052 findings finding NNS 1053 1060 suggest suggest VBP 1061 1065 that that IN 1066 1069 the the DT 1070 1080 processing processing NN 1081 1083 of of IN 1084 1088 p105 p105 NN 1089 1091 is be VBZ 1092 1099 subject subject JJ 1100 1102 to to TO 1103 1111 negative negative JJ 1112 1122 regulation regulation NN 1123 1125 by by IN 1126 1129 the the DT 1130 1137 various various JJ 1138 1147 NF-kappaB nf-kappab NN 1148 1156 subunits subunit NNS 1156 1157 . . . 1158 1160 We we PRP 1161 1168 further further RB 1169 1180 demonstrate demonstrate VBP 1181 1185 that that IN 1186 1190 p105 p105 NN 1191 1200 undergoes undergo VBZ 1201 1212 degradation degradation NN 1213 1215 in in IN 1216 1245 lipopolysaccharide-stimulated lipopolysaccharide-stimulated JJ 1246 1251 human human JJ 1252 1261 monocytic monocytic JJ 1262 1267 cells cell NNS 1267 1268 . . . 1269 1276 However however RB 1276 1277 , , , 1278 1281 the the DT 1282 1291 inducible inducible JJ 1292 1303 degradation degradation NN 1304 1306 of of IN 1307 1311 p105 p105 NN 1312 1314 is be VBZ 1315 1318 not not RB 1319 1326 coupled couple VBN 1327 1331 with with IN 1332 1335 the the DT 1336 1346 generation generation NN 1347 1349 of of IN 1350 1353 p50 p50 NN 1353 1354 . . . 1355 1363 Together together RB 1363 1364 , , , 1365 1370 these these DT 1371 1378 studies study NNS 1379 1390 demonstrate demonstrate VBP 1391 1395 that that IN 1396 1399 the the DT 1400 1410 processing processing NN 1411 1414 and and CC 1415 1424 inducible inducible JJ 1425 1436 degradation degradation NN 1437 1439 of of IN 1440 1444 p105 p105 NN 1445 1448 are be VBP 1449 1463 differentially differentially RB 1464 1473 regulated regulate VBN 1473 1474 . . .